Is ERAS p.Arg32His (c.95G>A) pathogenic?

ERAS p.Arg32His (c.95G>A) is classified Uncertain significance in ERAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-06). AlphaMissense: likely benign (0.0997); Ultra-rare (popmax 0.0209%, eas).

How common is ERAS p.Arg32His (c.95G>A) in the general population?

ERAS p.Arg32His (c.95G>A) is ultra-rare (popmax 0.0209%, eas) (gnomAD).

What do computational predictors say about ERAS p.Arg32His (c.95G>A)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

ERAS p.Arg32His

c.95G>A · rs782770684 · VCV2514123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP -4.1
Regional constraint	o/e 0.69	unconstrained · MANE · 698 bp · p 1e-05 · regional, not allelic
Overall
CADD	12.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% East Asian · 7/33,498 alleles

Filtering AF 0.00975% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00695%

Overall 0.00336% 40/1,189,781 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0209%	4,785
South Asian	0.0152%	6,598
Finnishnot grpmax-eligible	0.0109%	9,165
African / African-American	0.00524%	19,092
Admixed American	0.00453%	22,062
Remaining individualsnot grpmax-eligible	0.00427%	23,393
European (non-Finnish)	0.00147%	68,003

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERAS
Protein: p.Arg32His
Coding: c.95G>A
MANE Select: NM_181532
dbSNP: rs782770684
Type: single nucleotide variant
Location: chrX:48829218 (GRCh38)
Structure: AlphaFold pLDDT 79.71

Full ERAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERAS p.Gly118= Benign ★★ same type
ERAS p.Ala121Thr Uncertain significance ★ same type
ERAS p.Ala15Val Uncertain significance ★ ⚠ same type
ERAS p.Ala165Thr Uncertain significance ★ ⚠ same type
ERAS p.Ala175Thr Uncertain significance ★ ⚠ same type
ERAS p.Arg220Trp Uncertain significance ★ ⚠ same type
ERAS p.Cys215Tyr Uncertain significance ★ ⚠ same type
ERAS p.Gln186Arg Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/eras-p-arg32his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown